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Context First-degree relatives of women with polycystic ovary syndrome (PCOS) present hormonal and metabolic alterations compared to girls unrelated to PCOS. It is unknown whether glucose intolerance in the PCOS proband confers a more severe metabolic predisposition on their first-degree relatives. Objective To determine whether glucose tolerance status in women with PCOS is associated with worsened glucose metabolism and sex hormone levels in their peripubertal daughters or sisters. Design Cross-sectional study. Setting Seven academic centers in North America, South America, and Europe. Patients Sixty-four pairs of women with PCOS and their daughters or younger sisters aged between 8 and 14 years were recruited. Twenty-five mothers or older sisters with PCOS were glucose intolerant (GI) and 39 were normal glucose tolerant (NGT). Main Outcome Measures Beta-cell function estimated by the insulin secretion-sensitivity index-2 (ISSI-2) during an oral glucose tolerance test and by the disposition index during a frequently sampled IV glucose tolerance test. Free testosterone and 17-hydroxyprogesterone (17-OHP) levels. Results Being related to a GI PCOS proband was associated with a lower ISSI-2 (P-value = 0.032) after adjusting for ethnicity, body mass index z-score, and pubertal stage. They also had higher free testosterone (P-value = 0.011) and 17-OHP levels compared to girls with an NGT proband, the latter becoming significant after adjusting for confounders (P-value = 0.040). Conclusions Compared to first-degree female relatives of women with PCOS and NGT, first-degree relatives of women with PCOS and GI display lower beta-cell function and hyperandrogenemia, putting them at higher risk of GI and PCOS development.

Due to its simplicity, time-limited eating (TLE) may represent a more feasible approach for treating adolescents with obesity compared to other caloric restriction regimens. This pilot study examines the feasibility and safety of TLE combined with continuous glucose monitoring (CGM) in adolescents. Fifty adolescents with BMI ≥95th percentile were recruited to complete a 12-week study. All received standard nutritional counseling, wore a CGM daily, and were randomized to: (1) Prolonged eating window: 12 h eating/12 h fasting + blinded CGM, (2) TLE (8 h eating/16 h fasting, 5 days per week) + blinded CGM, (3) TLE + real-time CGM feedback. Recruitment, retention, and adherence were recorded as indicators of feasibility. Weight loss, dietary intake, physical activity, eating behaviors, and quality of life over the course of the intervention were explored as secondary outcomes. Forty-five participants completed the study (16.4 ± 1.3 years, 64% female, 49% Hispanic, 75% public insurance). There was high adherence to prescribed eating windows (TLE 5.2 d/wk [SD 1.1], control 6.1 d/wk [SD 1.4]) and daily CGM wear (5.85 d/wk [SD 4.8]). Most of the adolescents (90%) assigned to TLE reported that limiting their eating window and wearing a CGM was feasible without negative impact on daily functioning or adverse events. There were no between-group difference in terms of weight loss, energy intake, quality of life, physical activity, or eating behaviors. TLE combined with CGM appears feasible and safe among adolescents with obesity. Further investigation in larger samples, with a longer intervention duration and follow-up assessments are needed.

Background: Time Limited Eating (TLE) is an effective strategy for management of obesity in adults, but there is a paucity of data that have examined its use in the clinical management of children with obesity. A TLE approach involves interspersing normal daily caloric intake with periods of prolonged calorie restriction several times per week. TLE may actually be more feasible, non-stigmatizing, flexible and effective in children, especially for adolescents, compared to alternatives like daily caloric or macronutrient restriction. This is because TLE removes the need for intensive counting of daily calorie intake or macronutrient content and focuses on a straightforward task of consuming food during a pre-specified time period. Also it avoids periods of extended caloric restriction which may interfere with growth and/or risk evoking development of eating behaviors. This case series describes four patients who trialed a TLE approach in a clinical weight management clinic and describes BMI reduction at 4 months. Case Presentation: To date, 4 patients, ages 5-15, with varying underlying pathologies (i.e. Bardet Biedl Syndrome (BBS), previously healthy, craniopharyngioma and epilepsy) have tried a TLE type approach (16-hour fast/8-hour feed for 3-5 days per week) for 4 months and have demonstrated an average decrease in their BMI z-score compared to baseline of -0.24 SD. Patients and their families reported high degrees of satisfaction with this dietary approach. Conclusions: Families were very satisfied with the TLE intervention and reported it was feasible, flexible and sustainable to implement in a real life setting and associated with decreased zBMI. Further investigation is required to determine if this approach is effective in both the short and long term as a weight management technique.

Objective: To examine the prospective associations between exposure to perfluoroalkyl substances (PFASs) and longitudinal measurements of glucose metabolism in high-risk overweight and obese Hispanic children. Methods: Forty overweight and obese Hispanic children (8–14 years) from urban Los Angeles underwent clinical measures and 2-hour oral glucose tolerance tests (OGTT) at baseline and a follow-up visit (range: 1–3 years after enrollment). Baseline plasma perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS), and the plasma metabolome were measured by liquid-chromatography with high-resolution mass spectrometry. Multiple linear regression models were used to assess the association between baseline PFASs and changes in glucose homeostasis over follow-up. A metabolome-wide association study coupled with pathway enrichment analysis was performed to evaluate metabolic dysregulation associated with plasma PFASs concentrations. We performed a structural integrated analysis aiming to characterize the joint impact of all factors and to identify latent clusters of children with alterations in glucose homeostasis, based on their exposure and metabolomics profile. Results: Each ln (ng/ml) increase in PFOA and PFHxS concentrations was associated with a 30.6 mg/dL (95% CI: 8.8–52.4) and 10.2 mg/dL (95% CI: 2.7–17.7) increase in 2-hour glucose levels, respectively. A ln (ng/ml) increase in PFHxS concentrations was also associated with 17.8 mg/dL increase in the glucose area under the curve (95% CI: 1.5–34.1). Pathway enrichment analysis showed significant alterations of lipids (e.g., glycosphingolipids, linoleic acid, and de novo lipogenesis), and amino acids (e.g., aspartate and asparagine, tyrosine, arginine and proline) in association to PFASs exposure. The integrated analysis identified a cluster of children with increased 2-h glucose levels over follow up, characterized by increased PFAS levels and altered metabolite patterns. Conclusions: This proof-of-concept analysis shows that higher PFAS exposure was associated with dysregulation of several lipid and amino acid pathways and longitudinal alterations in glucose homeostasis in Hispanic youth. Larger studies are needed to confirm these findings and fully elucidate the underlying biological mechanisms. Keywords: Perfluoroalkyl substances, Type 2 diabetes, Glucose metabolism, Metabolomics, Children

OBJECTIVES: Pediatric Non-Alcoholic Fatty Liver Disease is prevalent among Hispanics, which may partially result from a higher frequency of the C > G polymorphism in the patatin-like phospholipase 3 (PNPLA3) gene. Our prior work showed an interaction between the GG genotype and high dietary sugar, resulting in higher liver fat. Additionally, studies show that extreme sugar depletion improves liver fat in children with obesity. This trial aimed to test whether a clinical intervention for sugar reduction versus standard diet advice in Hispanic youth differentially impacts liver fat, liver fibrosis, body weight and composition, and whether effects differed by PNPLA3 genotype. METHODS: Hispanic youth with obesity (n = 105; 72% GG) were randomized to a healthy eating control group or a sugar reduction group (goal, 0.05). No treatment by PNPLA3 genotype interaction was observed for any endpoint (P > 0.05). While there was no significant change in fat mass in either study arm, secondary analyses revealed that participants who reduced fat mass, significantly reduced liver fat compared to those without fat mass reduction [−1.8% (−6.2, −3.4) vs. 0.3% (−1.0, 1.1), P

Background: One limitation to studying time limited eating (TLE) in adolescents is difficulty in reliably assessing adherence to fasting periods. Dietary recalls, which are currently used to monitor diet adherence, have been criticized due to potential error in reporting, omission bias and suboptimal compliance. Continuous glucose monitoring (CGM) may be a useful tool to overcome these barriers; however, it requires daily wear and understanding of expected glycemic excursions. The present study examines the feasibility of daily CGM use and its utility as a tool to monitor adherence to fasting periods in a diverse cohort of adolescents with obesity participating in a pilot study of 8-hour TLE. Methods: Twenty adolescents (mean age 16.0+1.3 years, 70% female, 55% Latinx, 75% public insurance) with BMI ≥ 95th percentile, were enrolled in a 12-week study and randomized to: (1) Group 1 (control schedule): 12-hour eating period + blinded CGM, (2) Group 2 (TLE schedule): 8-hour eating period + blinded CGM, or (3) Group 3: 8-hour eating period + CGM with real-time feedback. CGM wear time was calculated as the actual weekly wear time divided by the prescribed wear time. At weeks 0, 4 and 12, CGM data from 7 days of self-reported fasting periods were reviewed to evaluate any glycemic excursions >50 ng/dL. Results: Overall, the mean CGM wear time was 90% (35-100%) with no difference between intervention arms. During self-reported fasting periods, only 4 adolescents had excursions >50 ng/dL, one of whom was diagnosed with type 2 diabetes. The remaining 16 participants had no excursions >50 ng/dL during their fasting periods. Conclusions: These data suggest that CGM may be a feasible tool to monitor adherence to TLE and provide a more accurate assessment of true fasting periods with less opportunity for error and bias when compared to self-report. Larger studies are needed to validate these findings and further explore the use of CGM as a tool in obesity research in adolescents. Disclosure M. Naguib: None. M. I. Goran: None. J. Raymond: None. E. Hegedus: None. C. Wee: None. A. Vidmar: None.

Background Low-calorie sweeteners (LCSs) provide sweetness without sugar or calories and are used to replace added sugars by many children with type 1 diabetes (T1D). However, the role of LCSs in diabetes management and cardiometabolic health is unclear. Objective The Diabetes Research in Kids Study (DRINK-T1D) aims to investigate effects of LCS restriction on glycemic variability, visceral adiposity, lipid profiles, and systemic inflammation among children 6–12 years old with T1D. Methods Children with T1D, who report habitual consumption of foods and beverages containing LCSs, are recruited from the Washington Nationals Diabetes Care Complex (DCC) at Children's National Hospital (CNH) in Washington, DC. Following a phone screening and two-week run-in period involving continuation of usual LCS intake, children are randomized to 12 weeks of LCS restriction (replacement of diet beverages with still or sparkling water and avoidance of other sources of LCSs) or continued usual LCS intake (control). The primary outcome is the difference in change in glycemic variability in the LCS restriction group versus the control group. Change in glycemic variability will be assessed as the difference in daily average time-in-range (TIR), measured using continuous glucose monitoring (CGM) during two weeks at the end of the 12-week intervention, compared with during the two-week run-in period prior to randomization. Participants also complete a variety of anthropometric, metabolic, dietary, and behavioral assessments throughout the 14-week study. Conclusions DRINK-T1D is an innovative, randomized controlled trial, evaluating effects of LCS restriction on glycemic variability and cardiometabolic health in children with T1D. Findings of DRINK-T1D will support or challenge the common practice of recommending LCS use in this patient population and will have clinically relevant implications for pediatric T1D management. Trial Registration ClinicalTrials.gov Identifier NCT04385888 .

Context Studies in rodents and humans suggest that high-fructose corn syrup (HFCS)–sweetened diets promote greater metabolic dysfunction than sucrose-sweetened diets. Objective To compare the effects of consuming sucrose-sweetened beverage (SB), HFCS-SB, or a control beverage sweetened with aspartame on metabolic outcomes in humans. Methods A parallel, double-blinded, NIH-funded study. Experimental procedures were conducted during 3.5 days of inpatient residence with controlled feeding at a research clinic before (baseline) and after a 12-day outpatient intervention period. Seventy-five adults (18-40 years) were assigned to beverage groups matched for sex, body mass index (18-35 kg/m2), and fasting triglyceride, lipoprotein and insulin concentrations. The intervention was 3 servings/day of sucrose- or HFCS-SB providing 25% of energy requirement or aspartame-SB, consumed for 16 days. Main outcome measures were %hepatic lipid, Matsuda insulin sensitivity index (ISI), and Predicted M ISI. Results Sucrose-SB increased %hepatic lipid (absolute change: 0.6 ± 0.2%) compared with aspartame-SB (-0.2 ± 0.2%, P Conclusion Consumption of both sucrose- and HFCS-SB induced detrimental changes in hepatic lipid, insulin sensitivity, and circulating lipids, lipoproteins and uric acid in 2 weeks.

Background Prior epidemiological and animal work has linked in utero exposure to ambient air pollutants (AAP) with accelerated postnatal weight gain, which is predictive of increased cardiometabolic risk factors in childhood and adolescence. However, few studies have assessed changes in infant body composition or multiple pollutant exposures. Therefore, the objective of this study was to examine relationships between prenatal residential AAP exposure with infant growth and adiposity. Methods Residential exposure to AAP (particulate matter 2.5, PM10]; nitrogen dioxide [NO2]; ozone [O3]; oxidative capacity [Oxwt: redox-weighted oxidative potential of O3 and NO2]) was modeled by spatial interpolation of monitoring stations via an inverse distance-squared weighting (IDW2) algorithm for 123 participants from the longitudinal Mother’s Milk Study, an ongoing cohort of Hispanic mother-infant dyads from Southern California. Outcomes included changes in infant growth (weight, length), total subcutaneous fat (TSF; calculated via infant skinfold thickness measures) and fat distribution (umbilical circumference, central to total subcutaneous fat [CTSF]) and were calculated by subtracting 1-month measures from 6-month measures. Multivariable linear regression was performed to examine relationships between prenatal AAP exposure and infant outcomes. Models adjusted for maternal age, pre-pregnancy body mass index, socioeconomic status, infant age, sex, and breastfeeding frequency. Sex interactions were tested, and effects are reported for each standard deviation increase in exposure. Results NO2 was associated with greater infant weight gain (β = 0.14, p = 0.02) and TSF (β = 1.69, p = 0.02). PM10 and PM2.5 were associated with change in umbilical circumference (β = 0.73, p = 0.003) and TSF (β = 1.53, p = 0.04), respectively. Associations of Oxwt (pinteractions xwt was associated with attenuated infant length change among males (β = -0.60, p = 0.01), but not females (β = 0.16, p = 0.49); umbilical circumference among females (β = 0.92, p = 0.009), but not males (β = -0.00, p = 0.99); and CTSF among males (β = 0.01, p = 0.03), but not females (β = 0.00, p = 0.51). Conclusion Prenatal AAP exposure was associated with increased weight gain and anthropometric measures from 1-to-6 months of life among Hispanic infants. Sex-specific associations suggest differential consequences of in utero oxidative stress. These results indicate that prenatal AAP exposure may alter infant growth, which has potential to increase childhood obesity risk.

Objectives To identify dietary patterns associated with hepatic fat fraction (HFF), a measure of liver fat content and risk factor for non-alcoholic fatty liver disease, in a prospective study of 397 multi-ethnic youth. Methods We obtained information on habitual dietary intake via the Block Kids Food Frequency Questionnaire at age 6 to 15 years ('T1') and 12 to 19 years ('T2'), and measured HFF using magnetic resonance imaging at T2. We derived dietary patterns via principal components analysis and examined associations with ln-transformed HFF using linear regression models that accounted for maternal education, gestational diabetes exposure and smoking habits; and child pubertal status, BMI and physical activity. Results At T1, none of the dietary patterns identified were associated with HFF measured at T2. At T2, a Prudent dietary pattern characterized by high fruit and vegetable intake was inversely associated with HFF (-0.08 [95% CI: -0.16, -0.00]). Similarly, increased adherence to the Prudent pattern across T1 and T2 corresponded with lower ln-HFF (-0.11 [-0.18, -0.04] units). On the other hand, adherence to a Western pattern comprising fried foods and refined carbohydrates at T2 correlated with higher HFF among non-Hispanic White participants (0.16 [0.06, 0.26]). These findings persisted after accounting for child BMI. Conclusions Even in healthy youth, a diet high in fruits and vegetables is associated with lower HFF, whereas a diet high in fried foods and refined carbohydrates is related to higher HFF. Dietary changes may serve as an early preventive measure to mitigate liver fat accrual.

BACKGROUND: Time limited eating (TLE) has been shown to be effective for weight loss and improvement of glycemic control in adults with obesity and type 2 diabetes (T2D), but has not been well studied in adolescents. TLE may be a more feasible, flexible and effective dietary intervention for adolescents because it removes the need for intensive counting of calories or macronutrients, and emphasizes eating during a specified time period. OBJECTIVES: The aim of this study is to assess the feasibility of a TLE approach in adolescents with obesity using a continuous glucose monitor (CGM) to promote adherence to the intervention. METHODS: We propose a prospective, randomized controlled trial, in 60 adolescents (ages 14–18) with obesity (BMI% ≥ 95th percentile). Youth will be randomized to one of three treatment groups for a 12-week intervention: Group 1) Low sugar and carbohydrate education (LSC, 5% of total daily calories from sugar (< 35 g)/day; < 90 g carbohydrate (CHO)/day) + blinded CGM (used to monitor adherence and glycemic outcomes without real time feedback), Group 2) LSC + TLE (16-h fast/8-h feed for 5 days per week) + blinded CGM, and Group 3) LSC + TLE+ real time feedback via CGM (to evaluate effect of providing CGM data on intervention efficacy). Outcomes will include change in total body fat (TBF) percentage measured on DEXA scan, BMI status and fasting blood glucose at 12 weeks compared to baseline. CONCLUSIONS: TLE is a potentially powerful lifestyle intervention that could be readily integrated into pediatric weight management programs to optimize their impact and accelerate healthy changes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03954223

OBJECTIVES: To examine the extent to which non-nutritive sweetener (NNS; e.g., aspartame) intake during pregnancy is associated with offspring BMI z-score trajectory from birth to 15 years. METHODS: We included 1683 mother-child pairs from Project Viva, a prospective pre-birth-cohort recruited in 1999–2002 in Massachusetts. The main exposure was maternal NNS intake assessed in the 1(st) and 2(nd) trimesters of pregnancy using a food frequency questionnaire. We defined NNS as servings/day of diet soda + NutraSweet (aspartame packets) averaged across 1(st) and 2(nd) trimesters. We used linear regression models to examine associations of maternal NSS intake with offspring BMI z-score at each in-person research visit (birth, 6 months, 3 years, 7 years, and 12 years). We also used mixed-effects models to examine associations with BMI z-score trajectory from birth to 15 years, including both research and clinical measures of BMI for 1570 participants with ≥3 BMI z-score values. We adjusted all models for maternal pre-pregnancy BMI, age, race/ethnicity, education, parity, and pregnancy smoking status. RESULTS: 70% of mothers were white and mean (SD) pre-pregnancy BMI was 24.6 (5.2) kg/m2. Mean (SD; IQR) intake of NNS was 0.23 (0.55; 0.22) servings/day. While maternal NNS intake (per servings/day) was not associated with BMI z-score at birth (β −0.03 units; 95% CI −0.14, 0.08), NNS was associated with higher BMI z-score at 6 months (β 0.17; 0.06, 0.28), 3 years (β 0.13; 0.03, 0.24), 7 years (β 0.16; 0.04, 0.29) and 12 years (β 0.16; 0.01, 0.31). Based on the BMI z-score trajectory, the associations of NNS intake (Q4 vs. Q1) with BMI z-score became stronger with increasing age from 3–14 years (p(interaction) with age

Background Kiritimati is a remote Pacific Island estimated to have high rates of overweight/obesity (~ 81%) and type 2 diabetes (T2DM; ~27%), potentially related to high sugar consumption starting early in life. We aimed to determine the feasibility and effectiveness of a short-term dietary sugar-reduction intervention on sugar consumption and glucose control in Kiritimati adolescents. Methods A school-based pilot randomized controlled trial over two weeks. The two high schools on Kiritimati were randomized to the control school and the intervention school. Inclusion criteria was enrollment at one of the two high schools on the island. Exclusion criteria was age > 18 years. 63 students enrolled (n = 26 control; n = 37 intervention). The intervention consisted of installing a water filter at the school, providing reusable water bottles, and a 30-minute group dietary education session. Beverage frequency questionnaires and 24-hour diet recalls were conducted at baseline and follow-up. Continuous blood glucose monitors (CGMs; FreeStyle Libre Pro) measured indices of blood glucose control over 14 days (one-week pre-intervention, one-week post-intervention). A statistically significant effect of the intervention was considered a time x group interaction term of p interaction=0.001). However, there were no significant effects of the intervention on any of the CGM measures, which were normal at baseline. No adverse events were noted. Conclusions A 7-day sugar-reduction intervention significantly reduced sugar intake but had no effects on CGM measures in Kiritimati adolescents at high risk for obesity and T2DM. This pilot study suggests a simple sugar-reduction intervention could improve diet quality in adolescents on Pacific Islands with high rates of obesity/T2DM. Trial Registration: ClinicalTrials.gov NCT04319003. Registered March 24 2020 – retrospectively registered, clinicaltrials.gov/ct2/show/NCT04319003

Excess sugar intake increases risk for obesity and related comorbidities among children. The World Health Organization (WHO), American Heart Association (AHA) and the 2015 USDA dietary recommendations have proposed guidelines for added sugar intake to reduce risk for disease. WHO and USDA recommendations are presented as a percentage of daily calories from added sugar. This approach is not easily understood or translated to children, where energy needs increase with age. The AHA recommendation is based on a fixed value of 25 g of added sugar for all children 2-19 years of age. This approach does not take into account the different levels of intake across this wide age range. Due to these limitations, we adapted current recommendations for added sugars based on daily energy needs of children 2-19 years. We used those values to derive simple regression equations to predict grams or teaspoons of added sugars per day based on age that would be equivalent to 10% of daily energy needs. This proposed approach aligns with the changing nutritional needs of children and adolescents during growth.

Acculturation to the US culture is associated with suboptimal dietary choices in Latino youth. The role of parental education in shaping children’s nutrition is less clear. The purpose of this study was to examine the relationships between parental education, acculturation and dietary intake in 96 Latino youth ages 8–18 years. Parental education was assessed using a seven-category variable. Acculturation was assessed using the Acculturation, Habits, and Interests Multicultural Scale for Adolescents questionnaire. Dietary intake was assessed via 24-h dietary recalls using the multiple pass technique. Parental education was associated with lower fat intake (β = −0.115, p = 0.02) and lower fiber intake (β = 0.144, p = 0.03); these associations remained significant after controlling for age, sex, BMI and acculturation. There were no significant associations between acculturation and dietary variables (all p’s >0.05). This data suggests parental education may play an important role in shaping dietary intake in Latino youth.

BackgroundInfant cognitive development is influenced by maternal factors that range from obesity to early feeding and breast milk composition. Animal studies suggest a role for human milk oligosaccharide (HMO), 2'-fucosyllactose (2'FL), on learning and memory, yet no human studies have examined its impact on infant cognitive development relative to other HMOs and maternal factors.ObjectiveTo determine the impact of 2'FL from breast milk feeding on infant cognitive development at 24 months of age relative to maternal obesity and breast milk feeding frequency.Methods and materialsHispanic mother-infant pairs (N = 50) were recruited across the spectrum of pre-pregnancy BMI. Breast milk was collected at 1 and 6 months, and feedings/day were reported. Nineteen HMOs were analyzed using high-performance liquid chromatography, with initial interest in 2'FL. Infant cognitive development score was assessed with the Bayley-III Scale at 24 months. Linear regressions were used for prediction, and bootstrapping to determine mediation by 2'FL.ResultsMaternal pre-pregnancy BMI was not related to feedings/day or HMOs, but predicted poorer infant cognitive development (β = -0.31, P = 0.03). Feedings/day (β = 0.34) and 2'FL (β = 0.59) at 1 month predicted better infant cognitive development (both P≤ 0.01). The association of feedings/day with infant cognitive development was no longer significant after further adjustment for 2'FL (estimated mediation effect = 0.13, P = 0.04). There were no associations of feedings/day and 2'FL at 6 months with infant cognitive development.ConclusionsOur findings suggest that maternal factors influence infant cognitive development through multiple means. Though maternal obesity may be a separate negative influence, greater frequency of breast milk feeding at 1 month contributed to infant cognitive development through greater exposure to 2'FL relative to other HMOs. The influence of 2'FL was not significant at 6 months, indicating that early exposure to 2'FL may be a critical temporal window for positively influencing infant cognitive development.

Background Extant obesity efforts have had a limited impact among low-income underserved children, in part because existing programs are limited in terms of their short duration and low dosage, limited accessibility and sustainability; and failure to address barriers faced by diverse low-income families. Methods This two-arm, parallel, randomized controlled trial (RCT) tests whether delivering obesity prevention, as part of an ongoing home visitation program (HVP), is an effective approach for primary (infants) and secondary (mothers) obesity prevention among low-income, underserved families. This RCT further examines the role of maternal and social factors as key mechanisms of transmission of infants' obesity risk, and the real-life costs of delivering obesity prevention as part of HVPs. Specifically, 300 low-income mothers/infants (6mo at baseline) participating in the Healthy Families America home visitation program in Antelope Valley (CA) will be recruited and enrolled in the study. Home visitors serving families will be randomly assigned to deliver the standard HVP curriculum with or without obesity prevention as part of their weekly home visits for two years. Anthropometric, metabolic and behavioral assessments of mothers/infants will be conducted at enrollment and after 6 and 18 months of intervention. Discussion This study addresses the need to develop interventions targeting at-risk infants before they become obese. The proposed research is timely as the Institute of Medicine, the United States Department of Agriculture, and the Department of Health and Human Services are revising their recommendations to address key factors influencing obesity risk in children from birth to 24 months of age.

SummaryBackground Extant obesity efforts have had limited impact among low-income underserved children, in part because of limitations inherent to existing programs: (i) short duration and low intensity; (ii) late timing of implementation, when children are already overweight or obese; (iii) intervention delivery limiting their accessibility and sustainability; and (iv) failure to address barriers such as a lack of culturally competent services, poverty and housing instability, which interfere with healthy lifestyle changes. Objective This concept paper proposes an innovative model of obesity prevention implemented in infancy and sustained throughout early childhood to address the limitations of current obesity prevention efforts. Specifically, we propose to integrate sustained, weekly, in-home obesity prevention as part of the services already delivered by ongoing Home Visitation Programs, which currently do not target obesity prevention. Conclusion The home visiting structure represents an ideal model for impactful obesity prevention as home visitation programs: (i) already provide comprehensive services to diverse low-income infants and families who are most at risk for obesity and poor health because of socio-economic and structural conditions; (ii) services are initiated in infancy and sustained throughout critical developmental periods for the formation of healthy/unhealthy behaviors; and (iii) have been in place for more than 40 years, with a widespread presence across the United States and nationwide, which is critical for the scalability and sustainability of obesity prevention.

Objective T-lymphocytes are potential initiators and regulators of adipose tissue (AT) inflammation, but there is limited human data on omental AT. The aim of this study was to assess the relationship between T cells, particularly Foxp3+ regulatory T (Treg) cells, in human subcutaneous (subQ) and omental AT and type 2 diabetes risk. Methods SubQ and deep subQ (DsubQ) abdominal and omental AT biopsies were collected from 44 patients (body mass index, BMI ≥25) undergoing elective abdominal surgery. Flow cytometry was used to quantify CD4+ T cell (T effector and Treg) and macrophages (M1 and M2), and systemic inflammation was measured in fasting blood. Results Tregs were significantly lower in omental versus subQ and DsubQ AT, and M1 cell counts were significantly higher in the omental and DsubQ depot relative to the subQ. Only omental AT Tregs were negatively associated with fasting glucose and MCP-1 and positively associated with homeostasis model assessment (HOMA)-β. M1 and M2 cell counts across multiple depots had significant relationships with HOMA-insulin resistance, tumor necrosis factor-α, insulin, and HOMA-β. All relationships were consistent across ethnicities. Conclusions Tregs were significantly lower in omental versus both subQ adipose depots. Fewer omental Tregs may have metabolic implications based on depot-specific relationships with higher fasting glucose and lower β-cell function.

BACKGROUND It is unknown to what extent higher maternal blood pressure (BP) in early postpartum impacts the relationship between higher maternal weight status and greater infant weight gain in early postpartum. OBJECTIVE To evaluate the mediating role of higher maternal BP at 1 month postpartum on the association between higher maternal weight status at 1 month postpartum and greater infant weight gain over 6 months postpartum. METHODS Participants were 169 Hispanic mother-infant pairs. Maternal body mass index (BMI) and BP were assessed at 1 month postpartum. Infant weight was measured at 1 and 6 months postpartum to calculate weight-for-age z scores (WAZ). Multiple linear regression models were used for prediction, and Sobel test was used to determine mediation. RESULTS Controlling for maternal pre-pregnancy BMI, age, delivery mode, infant sex, and infant birth weight revealed that both maternal BMI (β = .29) and BP (β = .32) predicted infant WAZ gain (both P ≤ .03). However, the relationship between infant WAZ gain and maternal BMI was no longer significant after further adjustment for maternal BP, which remained significant (P < .05). Maternal BP explained 23.6% (Sobel T = 2.01) of the association between maternal BMI at 1 month and infant WAZ gain over 6 months. CONCLUSION Our data suggest that higher maternal weight status at 1 month postpartum is related to greater infant weight gain over 6 months postpartum, and this relationship is mediated by higher maternal BP at 1 month postpartum.

Objective Circulating cytokines are frequently cited as contributors to insulin resistance in children with obesity. This study examined whether circulating adipocytokines, independent of adiposity, predicted pubertal changes in insulin sensitivity (SI), insulin secretion (AIR), and β-cell function in high-risk adolescents. Methods 158 Hispanic adolescents with overweight or obesity were followed for a median of 4 years. Adipocytokines were measured using Luminex technology. SI, AIR, and the disposition index were derived from an intravenous glucose tolerance test and minimal modeling. Total fat mass was measured by DXA and visceral adipose tissue (VAT) by MRI. Results Surprisingly, mean IL-8, IL-1β, IL-6, and TNF-α decreased between 5% and 6.5% per year from baseline (P

Summary Objective The objective of this study was to examine the relationship between diet and inflammation, and adiposity in minority youth. Design and Methods The study was designed as a cross-sectional analysis of 142 overweight (≥85th body mass index percentile) Hispanic and African–American adolescents (14–18 years) with the following measures: anthropometrics, adiposity via magnetic resonance imaging, dietary intake via 24-h dietary recalls, and inflammation markers from fasting blood draws utilizing a multiplex panel. Partial correlations were estimated and analysis of covariance (ancova) models fit to examine the relationship among dietary variables, inflammation markers and adiposity measures with the following a priori covariates: Tanner stage, ethnicity, sex, total energy intake, total body fat and total lean mass. Results Inference based on ancova models showed that the highest tertile of fibre intake (mean intake of 21.3 ± 6.1 g d−1) vs. the lowest tertile of fibre intake (mean intake of 7.4 ± 1.8 g d−1) was associated with 36% lower plasminogen activator inhibitor-1 (P = 0.02) and 43% lower resistin (P = 0.02), independent of covariates. Similar results were seen for insoluble fibre. No other dietary variables included in this study were associated with inflammation markers. Conclusions These results suggest that increases in dietary fibre could play an important role in lowering inflammation and therefore metabolic disease risk in high-risk minority youth.

Author(s): Alderete, Tanya L; Sattler, Fred R; Richey, Joyce M; Allayee, Hooman; Mittelman, Steven D; Sheng, Xia; Tucci, Jonathan; Gyllenhammer, Lauren E; Grant, Edward G; Goran, Michael I | Abstract: ObjectiveSalsalate treatment has well-known effects on improving glycemia, and the objective of this study was to examine whether the mechanism of this effect was related to changes in adipose tissue.MethodsA randomized double-blind and placebo-controlled trial in obese Hispanics (18-35 years) was conducted. The intervention consisted of 4 g day(-1) of salsalate (n = 11) versus placebo (n = 13) for 4 weeks. Outcome measures included glycemia, adiposity, ectopic fat, and adipose tissue gene expression and inflammation.ResultsIn those receiving salsalate, plasma fasting glucose decreased by 3.4% (P l 0.01), free fatty acids decreased by 42.5% (P = 0.06), and adiponectin increased by 27.7% (P l 0.01). Salsalate increased insulin AUC by 38% (P = 0.01) and HOMA-B by 47.2% (P l 0.01) while estimates of insulin sensitivity/resistance were unaffected. These metabolic improvements occurred without changes in total, abdominal, visceral, or liver fat. Plasma markers of inflammation/immune activation were unchanged following salsalate. Salsalate had no effects on adipose tissue including adipocyte size, presence of crown-like structures, or gene expression of adipokines, immune cell markers, or cytokines downstream of NF-κB with the exception of downregulation of IL-1β (P l 0.01).ConclusionsFindings suggest that metabolic improvements in response to salsalate occurred without alterations in adiposity, ectopic fat, or adipose tissue gene expression and inflammation.

Objective One hour (1-hr) glucose during an oral glucose tolerance test (OGTT) is an emerging biomarker for type 2 diabetes. We compared the predictive power of 1-hr glucose to traditional glycemic markers for prospectively identifying prediabetes in youth. Research design and methods Obese normoglycemic Latino youth (N = 116) were assessed at baseline for glycated hemoglobin (HbA1c), fasting, 1-hr, and 2-hr glucose during an OGTT and were followed for up to 8 yr for the development of prediabetes. Receiver operating characteristic (ROC) curves were used and a multivariable prediction model was developed. Results The area under the 1-hr glucose ROC curve was the most powerful predictor of prediabetes over time [0.73, 95% confidence interval (CI) = 0.64–0.83]. However, combining all indicators into a single model was superior to individual marker models (0.77, 95% CI = 0.690.86). Conclusions These results further support the utility of 1-hr glucose during an OGTT as a prospective marker of diabetes risk in youth.

There are limited data on the influence of vegetable consumption on adiposity and metabolic health, specifically nonstarchy vegetables and vegetables that are dark green and deep orange/yellow (also known as nutrient-rich vegetables). Our study examines the relationship between vegetable intake and adiposity, liver fat, and insulin dynamics in overweight Latino youth. This cross-sectional study of 175 overweight (body mass index ≥85th percentile) Latino youth (aged 8 to 18 years), with data collected during 2006-2011, included the following: dietary intake via multiple 24-hour recalls, total body fat via dual-energy x-ray absorptiometry, adipose tissue distribution and liver fat via magnetic resonance imaging, and insulin dynamics via frequently sampled intravenous glucose tolerance test. Linear regression and analysis of covariance were used for analysis, with the following a priori covariates: age, sex, energy intake, and total body fat. Participants who consumed the most nonstarchy vegetables (mean intake=1.7±1.0 servings/day) compared with the least (mean intake=0.1±0.1 servings/day) had 44% less liver fat (10.0%±8.5% vs 5.6%±8.7%; P =0.01). Nutrient-rich vegetable intake was positively correlated with insulin sensitivity ( r =0.19; P =0.03). Consumers of nutrient-rich vegetables (mean intake=0.3±0.4 servings/day [n=107]), compared with nonconsumers (n=68), had 31% increased insulin sensitivity (1.6±1.6 vs 2.1±1.3×10 –4 /min/μU/mL; P =0.03) and 17% less visceral adipose tissue (2.3±0.9 vs 1.9±0.7 L; P =0.01). Consumption of specific vegetable types by overweight Latino youth is associated with positive metabolic outcomes, including reduced visceral and liver fat and risk factors for type 2 diabetes, even when consumed in small quantities. These may be relevant targets for interventions.

Excessive consumption of added sugars negatively impacts metabolic systems; however, effects on cognitive function are poorly understood. Also unknown is whether negative outcomes associated with consumption of different sugars are exacerbated during critical periods of development (e.g., adolescence). Here we examined the effects of sucrose and high fructose corn syrup-55 (HFCS-55) intake during adolescence or adulthood on cognitive and metabolic outcomes. Adolescent or adult male rats were given 30-day access to chow, water, and either (1) 11% sucrose solution, (2) 11% HFCS-55 solution, or (3) an extra bottle of water (control). In adolescent rats, HFCS-55 intake impaired hippocampal-dependent spatial learning and memory in a Barne's maze, with moderate learning impairment also observed for the sucrose group. The learning and memory impairment is unlikely based on nonspecific behavioral effects as adolescent HFCS-55 consumption did not impact anxiety in the zero maze or performance in a non-spatial response learning task using the same mildly aversive stimuli as the Barne's maze. Protein expression of pro-inflammatory cytokines (interleukin 6, interleukin 1β) was increased in the dorsal hippocampus for the adolescent HFCS-55 group relative to controls with no significant effect in the sucrose group, whereas liver interleukin 1β and plasma insulin levels were elevated for both adolescent-exposed sugar groups. In contrast, intake of HFCS-55 or sucrose in adults did not impact spatial learning, glucose tolerance, anxiety, or neuroinflammatory markers. These data show that consumption of added sugars, particularly HFCS-55, negatively impacts hippocampal function, metabolic outcomes, and neuroinflammation when consumed in excess during the adolescent period of development.

Type 2 diabetes risk and its relationship to free fatty acid (FFA) exposure and visceral fat by prediabetes status in minority adolescents have yet to be explored. Therefore, the objective of this study was to examine the association of circulating FFA under varying conditions with prediabetes in Latino adolescents and to determine the relative relationships of FFA and visceral adiposity to insulin sensitivity, secretion, and β-cell function. Overweight or obese, but otherwise healthy Latino adolescent males and females (n = 164, 14.2 ± 2.5 years), were recruited for assessment of prediabetes, abdominal fat, and FFA levels taken at a fasting state (FFAF), during an OGTT (FFAOGTT), and overnight (FFANOCTURNAL). Prediabetic adolescents had a higher FFAF than those with normal glucose tolerance when controlling for age, sex, pubertal status, total percent body fat, and visceral fat. FFAOGTT and FFANOCTURNAL did not differ between participants with prediabetes and those with normal glucose tolerance after adjusting for covariates. Visceral fat was independently related to insulin sensitivity and secretion in pubertal adolescents; however, in post-pubertal adolescents, FFAF and visceral fat were both independent and negatively related to β-cell function. These results support a plausible progression of the lipotoxicity theory of diabetes development during the pubertal transition.

Objective: Obesity in childhood is associated with an inllammatory state in adipose tissue and liver, which elevates risk lor diabetes and liver disease. No prior study has examined associations between pathologies occurring in adipose tissue and liver to identily elements of tissue damage associated with type 2 diabetes risk, This study sought to determine whether inllammation and librosis in abdominal sub­ cutaneous adipose tissue (SAl) in obese/overweight children (BMI-z 2.3:': 0.76) was related to the extent of observed liver disease or type 2 diabetes risk, Methods: Biopsy samples 01 abdominal (SAl) and liver were simultaneously collected Irom 33 Italian children (mean BMI 28.1 :': 5.1 kg/m 2 and mean age 11.6:': 2.2 years) with confirmed NAFLD. Histology and immunohistochemistry were conducted on biopsies to assess inllammation and flbrosls in adipose tissue and fibrosis and inflammation in liver. Results: Presence vs. absence 01 crown-like structures (CLS) in SAT was signilicantly related to liver librosis scores (1.7:': 0.7 vs. 1.2:': 0.7, P ~ 0.04) independent 01 BMI. SAT librosis was significantly corre­ lated with a lower disposition index (r = -0.48, P = 0.006). No other adipose measures were associated with liver disease parameters. Conclusion: Markers of subcutaneous white adipose tissue inllammation are associated with greater extent 01 liver librosis independent of obesity and SAT fibrosis may contribute to diabetes risk through reduced insulin secretion.

SUMMARY: BACKGROUND: The effects of breastfeeding (BF) on metabolic syndrome (MetS) and diabetes mellitus in children exposed to gestational diabetes mellitus (GDM) in utero have rarely been evaluated. OBJECTIVE: This study assessed BF and GDM in relation to the prevalence of prediabetes and MetS in Hispanic children and adolescents (8–19 y). METHODS: This is a longitudinal study with 229 Hispanic children (8–13 y) with overweight/obesity, family history of diabetes, and an average of four annual visits (AV). Participants were categorized as follows: never (negative for prediabetes/MetS at all AVs), ever (positive for prediabetes/MetS at any visit), intermittent (positive for prediabetes/MetS at 1–2 AVs), and persistent (positive for prediabetes/MetS at greater than or equal to 3 AVs). RESULTS: Compared with GDM offspring who were not BF (referent), GDM offspring who were BF had lower odds of persistent prediabetes (OR = 0.18; 95% CI, 0.040–82; P = 0.02) and MetS (OR = 0.10; 95% CI, 0.02–0.55; P = 0.008). Compared with referent group, non-GDM offspring who were BF, and non-GDM offspring not BF had lower odds of persistent prediabetes (OR = 0.10; 95% CI, 0.03–0.39; P = 0.001; OR = 0.05; 95% CI, 0.01–0.11; P < 0.001) and MetS (OR = 0.14; 95% CI, 0.04–0.59; P = 0.01 and OR = 0.04; 95% CI, 0.01–0.11; P < 0.001). CONCLUSIONS: These results show BF is protective against prediabetes and MetS in offspring regardless of GDM status.

Exposure to man-made combustion products, including secondhand tobacco smoke, maternal smoking during pregnancy, and near-roadway air pollution (NRAP), have been associated with increased body mass index and obesity in children and have been shown to result in excess weight gain in animal models. Potential mechanisms include pro-inflammatory central nervous system effects of airborne particles on appetite control, resulting in increased caloric intake, or changes in basal metabolism due to effects on mitochondria and brown adipose tissue. Combustion-derived polyaromatic hydrocarbons have also been linked to altered lipid metabolism, epigenetic effects on PPARγ expression, particle-induced estrogenic effects, and alterations in the distribution of visceral fat. Emerging evidence that a broad spectrum of environmental chemicals have “obesogenic” properties and alter the metabolic profile of adipose tissue challenges the prevailing model that the childhood obesity epidemic is explained solely by increased caloric density of food and decreased physical activity. Research on environmental obesogens could identify novel targets for intervention and yield public health benefits, since NRAP and SHS exposure are both common in populations most at-risk for development of obesity.

Results: Comparing HC with NF, SI was inversely associated with activation in the anterior cingulate (r 2 = 0.65; P < 0.05), the insula (r 2 = 0.69; P < 0.05), the orbitofrontal cortex (r 2 = 0.74; P < 0.05), and the frontal and rolandic operculum (r 2 = 0.76; P < 0.001). Associations remained significant after adjustment for body mass index. Association of fasting insulin and cerebral activation disappeared after adjustment for waist circumference. Conclusion: In addition to weight loss, insulin sensitivity may pose an important target to regulate neural responses to food cues in the prevention of excessive weight gain.

Objective To investigate the impact of eating frequency on dietary intake, physical activity (PA), metabolic, and adiposity measures in minority youth. Methods This analysis included 185 overweight (≥85th BMI percentile) Hispanic and African-American youth (8-18 years) with the following cross-sectional measures: height, weight, BMI, dietary intake, body composition, metabolic parameters, PA, visceral adipose tissue (VAT), and subcutaneous adipose tissue. Each eating occasion (EO) was defined as ≥50 calories and ≥15 minutes from any previous EO. Participants were dichotomized based on EOs per 24-h into meal skippers

OBJECTIVE Little attention has been paid to possible intrinsic biological mechanisms for the decline in physical activity that occurs during puberty. This longitudinal observational study examined the association between baseline insulin sensitivity (SI) and declines in physical activity and increases in sedentary behavior in peripubertal minority females over a year. RESEARCH DESIGN AND METHODS Participants were Hispanic and African American girls (n = 55; 76% Hispanic; mean age 9.4 years; 36% obese). SI and other insulin indices were measured at baseline using the frequently sampled intravenous glucose tolerance test. Physical activity was measured on a quarterly basis by accelerometry and self-report. RESULTS Physical activity declined by 25% and time spent in sedentary behaviors increased by ∼13% over 1 year. Lower baseline SI predicted the decline in physical activity measured by accelerometry, whereas higher baseline acute insulin response to glucose predicted the decline in physical activity measured by self-report. Time spent in sedentary behavior increased by ~13% over 1 year, and this was predicted by lower baseline SI. All models controlled for adiposity, age, pubertal stage, and ethnicity. CONCLUSIONS When evaluated using a longitudinal design with strong outcome measures, this study suggests that lower baseline SI predicts a greater decline in physical activity in peripubertal minority females.

Objective Cortisol has been associated with preferential visceral adipose tissue (VAT) deposition; however, findings in humans are mixed, which may be clarified when diet is considered. Design and Methods Participants included 165 African-American and Latino, overweight adolescents (BMI% 97.2±3.2%, ages 13-18, 67% Latino, 66% female). Body composition was determined by dual energy X-ray absorptiometry, abdominal fat depots [VAT, subcutaneous (SAT)] by multiple-slice MRI, time-controlled serum sample to measure cortisol, and 2-day multi-pass 24-hour dietary recall. Linear regression analysis examined the cross-sectional relationship between cortisol, and the interaction of diet and cortisol on adiposity measures. Sex, race, age, and total body fat were a priori covariates. Results There was a significant interaction between cortisol and sugar (total and added) in the prediction of VAT (Pinteraction ≤ 0.05). Amongst participants with high total or added-sugar intake, cortisol was significantly associated with VAT (s = 0.031 P

Blunted diurnal cortisol variation has been associated with overt cardiovascular disease in adults. The relationship between the diurnal cortisol variation and subclinical atherosclerosis in youth has yet to be investigated. The objectives of this study were to (1) determine the relationship between overnight cortisol measures and CIMT in overweight and obese, African-American and Latino children; (2) assess ethnic differences in these relationships; and (3) explore whether overnight cortisol and CIMT relationships were independent of inflammatory markers, C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-∝ (TNF-∝).One hundred fifty-six overweight and obese African-American and Latino children (ages 8-17, 86 M/70 F, 55 African-American/101 Latino) underwent measures of CIMT by B-mode ultrasound, nocturnal cortisol rise (NCR = salivary cortisol rise from 2200 h to awakening at 0530 h), cortisol awakening response (CAR = salivary cortisol from time of awakening to 30 min later), fasting serum cortisol and overnight urinary free cortisol.Using linear regression, salivary cortisol(0530 h) and NCR were negatively associated with CIMT (β(standardized) = -0.215 and -0.220, p0.01) independent of age, height, percent body fat, ethnicity and systolic blood pressure. Nocturnal salivary cortisol(2200 h), morning serum cortisol, and overnight urinary free cortisol were not associated with CIMT. Using ANCOVA, participants with LOW NCR (NCR0.44 μg/dL, n = 52) had significantly greater CIMT than those with HIGH NCR (NCR ≥ 0.91 μg/dL, n = 52; 0.632 ± 0.008 vs. 0.603 ± 0.008 mm, p=0.01) after controlling for covariates. Ethnicity was independently associated with CIMT, whereby African-American children had greater CIMT than Latino children (-0.028 ± 0.009, p=0.006). The relationships between cortisol measures and CIMT did not differ between the two ethnic groups (all p(interaction) = 0.28-0.97). CRP, IL-6 and TNF-∝ were not associated with CIMT (p0.05). IL-6 was inversely related to NCR (r = -0.186, p = 0.03), but it did not explain the relationship between NCR and CIMT.Salivary cortisol(0530 h) and NCR, but not CAR, nocturnal salivary cortisol(2200 h), morning serum cortisol or overnight urinary free cortisol were associated with CIMT, independent of relevant covariates, including inflammatory factors. A low awakening salivary cortisol or a blunted NCR may be related to increased atherosclerosis risk in overweight and obese minority youth. These findings support adult studies suggesting flattened daytime diurnal cortisol variation impacts cardiovascular disease risk.

Objective Genetic variation in six genes has been associated with elevated liver fat and nonalcoholic fatty liver disease in adults. The influence of these genes on liver fat and whether a genetic risk score (GRS) would improve upon the ability of common clinical risk factors to predict elevated liver fat content (ELF) in Hispanic children was determined. Design and Methods 223 obese Hispanic children were genotyped for six SNPs. MRI was used to measure liver fat. A GRS was tested for association with ELF using multivariate linear regression. Predictors were assessed via ROC curves and pair-wise analysis was used to determine significance alone and combined with clinical markers. Results Only variants in PNPLA3 and APOC3 genes were associated with liver fat (P

Summary Purpose: Insulin responses to oral and intravenous glucose markedly differ by ethnicity. This study examined whether ethnic differences in pancreatic insulin secretion, hepatic insulin extraction and clearance explain these disparate findings in 35 obese African–American and 41 Latina girls (Tanner Stages: IV–V; ages: 14–18; body mass index percentile: 85.9–99.8%). Methods: Pancreatic insulin secretion, hepatic insulin extraction and clearance were estimated by C-peptide and insulin modeling during an oral glucose tolerance test. Insulin sensitivity (SI), acute insulin response to glucose (AIRG) and disposition index were derived from a frequently sampled intravenous glucose tolerance test. Results: Compared to Latinas, obese African–American adolescents had lower pancreatic insulin secretion (21.3%; P 0.05). Conclusions: Compensatory mechanisms to insulin resistance do not appear to explain the ethnic differences in insulin responses to oral and intravenous glucose in obese African–American and Latina girls.

Obesogens are compounds that disrupt the function and development of adipose tissue or the normal metabolism of lipids, leading to an increased risk of obesity and associated diseases. Evidence for the adverse effects of industrial and agricultural obesogens, such as tributyltin, bisphenol A and other organic pollutants is well-established. Current evidence suggests that high maternal consumption of fat promotes obesity and increased metabolic risk in offspring, but less is known about the effects of other potential nutrient obesogens. Widespread increase in dietary fructose consumption over the past 30 years is associated with chronic metabolic and endocrine disorders and alterations in feeding behaviour that promote obesity. In this Perspectives, we examine the evidence linking high intakes of fructose with altered metabolism and early obesity. We review the evidence suggesting that high fructose exposure during critical periods of development of the fetus, neonate and infant can act as an obesogen by affecting lifelong neuroendocrine function, appetite control, feeding behaviour, adipogenesis, fat distribution and metabolic systems. These changes ultimately favour the long-term development of obesity and associated metabolic risk.

OBJECTIVE In adults, 1-h glucose during an oral glucose tolerance test (OGTT) predicts the development of type 2 diabetes independent of fasting and 2-h glucose concentrations. The purpose of the current investigation was to examine the utility of elevated 1-h glucose levels to prospectively predict deterioration in β-cell function and the development of prediabetes in high-risk youth. RESEARCH DESIGN AND METHODS Obese Latino youth with a family history of type 2 diabetes (133 male and 100 female; age 11.1 ± 1.7 years) completed a baseline OGTT and were divided into two groups based upon a 1-h glucose threshold of 155 mg/dL ( RESULTS Over time, the ≥155 mg/dL group exhibited a significantly greater decline in β-cell function compared with youth with a 1-h glucose CONCLUSIONS These data suggest that a 1-h glucose ≥155 mg/dL during an OGTT is an independent predictor of β-cell deterioration and progression to prediabetes among obese Latino youth.

Evidence suggests that ambient air pollution (AAP) exposure may contribute to the development of obesity and type 2 diabetes. The objective of this study was to determine whether exposure to elevated concentrations of nitrogen dioxide (NO2) and particulate matter with aerodynamic diameter